Immunohistochemical Study on O-GlcNAcylation in Diabetic Pathologies: Molecular Mechanisms and Implications

Yoshihiro Akimoto; Yuri Miura; Akihiko Kudo; Hiroki Tsumoto; Toshiyuki Fukutomi; Daisuke Sugahara; Tomio Arai; Yuko Chiba; Shinya Kaname; Kunimasa Yan; Hayato Kawakami; Tamao Endo

doi:10.1267/ahc.25-00022

Yoshihiro Akimoto, Yuri Miura, Akihiko Kudo, Hiroki Tsumoto, Toshiyuki Fukutomi, Daisuke Sugahara, Tomio Arai, Yuko Chiba, Shinya Kaname, Kunimasa Yan, Hayato Kawakami, Tamao Endo

Author information

Yoshihiro Akimoto
Department of Microscopic Anatomy, Kyorin University School of Medicine
Yuri Miura
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology
Akihiko Kudo
Department of Microscopic Anatomy, Kyorin University School of Medicine
Hiroki Tsumoto
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology
Toshiyuki Fukutomi
Department of Pharmacology and Toxicology, Kyorin University School of Medicine
Daisuke Sugahara
Department of Microscopic Anatomy, Kyorin University School of Medicine
Tomio Arai
Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
Yuko Chiba
Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
Shinya Kaname
Department of Nephrology and Rheumatology, Kyorin University School of Medicine
Department of Internal Medicine, Kichijoji Asahi Hospital
Kunimasa Yan
Department of Pediatrics, Kyorin University School of Medicine
Hayato Kawakami
Department of Microscopic Anatomy, Kyorin University School of Medicine
Tamao Endo
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology

Keywords: diabetes, O-GlcNAcylation, vascular smooth muscle cell, diabetic nephropathy, O-phosphorylation

JOURNAL OPEN ACCESS Advance online publication

Article ID: 25-00022

DOI https://ntrd-jsjc-gov-cn-s-1416.res.gxlib.org.cn:443/rwt/1416/https/MSYXTLUQPJUB/10.1267/ahc.25-00022

Details

Abstract

O-linked N-acetylglucosamine (O-GlcNAc) modification, known as O-GlcNAcylation, is a dynamic post-translational modification involving the addition of N-acetylglucosamine to ser‍ine or threonine residues. It has emerged as a critical regulator in diabetic pathophysiology. This review summarizes current research on the role of O-GlcNAcylation in hyperglycemia-induced cellular dysfunction, and focuses on vascular smooth muscle cells, renal cytoskeletal proteins, and diabetic complications in animal and human models. Studies reveal that hyperglycemia upregulates O-GlcNAc transferase activity, disrupting the interplay between glycosylation and phosphorylation, thereby impairing signaling pathways and exacerbating vascular proliferation and renal cytoskeletal disorganization. Notable findings include the imbalance of β-actin modifications in diabetic nephropathy, correlated with podocyte damage and glomerular abnormalities. By elucidating these mechanistic pathways, this review underscores the potential of O-GlcNAcylation as a biomarker and a therapeutic target. Future research should focus on tissue-specific effects and pharmacological strategies that mitigate diabetes-induced complications while preserving normal cellular functions.

Corresponding author

Register with J-STAGE for free!